Chang Le, Sun Zhen, Zeng Shiyong, Huang Canyang, Cai Zhenyu
Department of Clinical Medicine, Quanzhou Medical College, Quanzhou, Fujian, People's Republic of China.
Medical Research Center of Quanzhou Medical College, Quanzhou, Fujian, People's Republic of China.
J Pain Res. 2024 Dec 14;17:4277-4288. doi: 10.2147/JPR.S491626. eCollection 2024.
This study employed Mendelian randomization (MR) analysis to confirm the causal effects of mental disorders on fibromyalgia.
The summary data for exposures, mediator, and outcome were extracted from the GWAS catalog project, IEU openGWAS project, and Finn biobank database. Significantly associated and independent single-nucleotide polymorphisms (SNPs) meeting the criteria of p < 5×10-8, r2 < 0.001, and kb = 10,000 were selected for MR analysis. We used univariate and multivariate Mendelian randomization (i) to investigate the causal relationship between mental disorders/insomnia and fibromyalgia and (ii) to examine the mediating role of insomnia. The inverse variance weighted (IVW) method along with other MR methods was employed for analysis, while sensitivity analyses were conducted to assess reliability and stability.
The results provided strong evidence to confirm the causal and positive associations between depression (OR = 6.749; 95% CI: 2.293-19.868, P = 0.001), irritability (OR: 1.873, 95% CI: 1.023-3.428, P = 0.042), insomnia (OR: 8.395, 95% CI: 1.384-50.931, P = 0.021), and fibromyalgia. Moreover, a positive causal relationship was detected between depression (OR = 1.230; 95% CI: 1.178-1.285; P < 0.001), irritability (OR = 1.084; 95% CI: 1.046-1.122; P < 0.001) and insomnia. Multivariate Mendelian randomization analysis showed that insomnia mediated the effects of depression and irritability on fibromyalgia, and the proportion of insomnia-mediated cases ranged from 25.2% to 26%.
This study showed a positive causal relationship between depression, irritability, insomnia, and fibromyalgia. Insomnia partly mediates this overall effect. Understanding the causal relationship between mental disorders and fibromyalgia and the mediating role of insomnia may provide more information for fibromyalgia intervention and prevention strategies.
本研究采用孟德尔随机化（MR）分析来证实精神障碍对纤维肌痛的因果效应。
从全基因组关联研究（GWAS）目录项目、IEU开放GWAS项目和芬兰生物银行数据库中提取暴露、中介变量和结局的汇总数据。选择符合p < 5×10-8、r2 < 0.001和kb = 10,000标准的显著相关且独立的单核苷酸多态性（SNP）进行MR分析。我们使用单变量和多变量孟德尔随机化（i）研究精神障碍/失眠与纤维肌痛之间的因果关系，以及（ii）检验失眠的中介作用。采用逆方差加权（IVW）方法及其他MR方法进行分析，并进行敏感性分析以评估可靠性和稳定性。
结果提供了有力证据，证实抑郁（比值比[OR] = 6.749；95%置信区间[CI]：2.293 - 19.868，P = 0.001）、易怒（OR：1.873，95% CI：1.023 - 3.428，P = 0.042）、失眠（OR：8.395，95% CI：1.384 - 50.931，P = 0.021）与纤维肌痛之间存在因果及正向关联。此外，还检测到抑郁（OR = 1.230；95% CI：1.178 - 1.285；P < 0.001）、易怒（OR = 1.084；95% CI：1.046 - 1.122；P < 0.001）与失眠之间存在正向因果关系。多变量孟德尔随机化分析表明，失眠介导了抑郁和易怒对纤维肌痛的影响，失眠介导的病例比例在25.2%至26%之间。
本研究表明抑郁、易怒、失眠与纤维肌痛之间存在正向因果关系。失眠部分介导了这一总体效应。了解精神障碍与纤维肌痛之间的因果关系以及失眠的中介作用，可能为纤维肌痛的干预和预防策略提供更多信息。
